Oxidants and mitogenesis as causes of mutation and cancer: the influence of diet

Basic Life Sci. 1993;61:419-36. doi: 10.1007/978-1-4615-2984-2_37.


A very high level oxidative damage to DNA occurs during normal metabolism. In each rat cell, the steady-state level of this damage is estimated to be about 10(6) oxidative adducts, and about 10(5) new adducts are formed daily. This endogenous DNA damage appears to be a major contributor to cancer and aging. The oxidative damage rate in mammalian species with a high metabolic rate, short life span, and high age-specific cancer rate such as in rats is much higher than the rate in humans, long-lived mammals with a lower metabolic rate, and a lower age-specific cancer rate. It is argued that deficiency of micronutrients, that protect against oxidative DNA damage, is a major contributor to human cancer. Epidemiological studies, a large body of experimental evidence, and theoretical work on the mechanisms of carcinogenesis point to mitogenesis as a major contributor to cancer. Dividing cells, compared to nondividing cells, are at an increased risk for mutations due to: 1.) conversion of DNA adducts to mutations; 2.) chance of mitotic recombination, gene conversion, and nondisjunction; and, 3.) increased exposure of DNA to mutagens. Mitogenesis also increases the probability of gene amplification and loss of 5-methylcytosine. Dietary interventions that lower mitogenesis, such as calorie restriction, decrease cancer incidence.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aging
  • Animals
  • Carcinogens / toxicity*
  • Cell Division / drug effects
  • DNA Damage*
  • Diet*
  • Energy Intake
  • Humans
  • Mitogens / toxicity*
  • Mutagens / toxicity*
  • Neoplasms / chemically induced
  • Neoplasms / etiology*
  • Oxidants / toxicity*


  • Carcinogens
  • Mitogens
  • Mutagens
  • Oxidants